Cholesterol, Lipoprotein Metabolism And Steroids Flashcards
Organic compound with four fused rings arranged in a specific configuration (ABCD ring system)
Steroids
A subgroup of steroids with a hydroxyl group at the 3-position of the A-ring
Sterol
Cholesterol structure
HO-A ring-B ring-C ring-D ring-hydrocarbon tail
Is cholesterol hydrophilic or hydrophobic?
Hydrophobic
What is the major sterol in animal tissues?
Cholesterol
Cholesterol is a precursor for the synthesis of what 3 compounds?
Bile salts
Steroid hormones
Vitamin D
Cholesterol function
Essential structural component of animal cell membranes (30%)
required to maintain both membrane structural integrity and fluidity at different temperatures
Enables animal cells to dispense within cell shape in order to protect membrane integrity and cell viability
Components of lipid rafts formation to facilitate cell signaling
Where is free cholesterol found?
Membranes of animal cell membranes
Free cholesterol is..
Unesterified. Hydroxyl group on A-ring
Esterified cholesterol is…
Esterified, or cholesteryl ester. A-ring has a fatty acid attached to the Oxygen
Are esterified cholesterol in the membranes?
Nope
Where are esterified cholesterol found?
Plasma. Most plasma cholesterol is in this form.
What cells a can synthesize cholesterol?
Most, but significantly from Liver, Intestine, and steroidogenic tissues.
Steroidogenic=adrenal cortex, testes, ovaries
What organs controls the overall cholesterol homeostasis?
Liver (synthesis, distribution, and elimination)
Sources of liver cholesterol
De novo synthesis
Diet
HDLs
Routes for cholesterol clearance from the liver
Secretion into VLDL/LDL
What leads to gradual deposition of cholesterol in the tissues?
The balance between cholesterol influx and efflux isn’t precise
Where does the cholesterol typically deposit?
Endothelial linings of blood vessels
Lipid depositions over time leads to
Plaque formation
Plaque formation, from lipid deposition, causes what?
Atherosclerosis. The narrowing of blood vessels
Atherosclerosis is important because
It causes an increased risk of cardio, cerebro, and peripheral vascular disease
May be life-threatening.
Substrates for Cholesterol Synthesis
Acetyl CoA
NADPH
ATP
cholesterol synthesis will occur under what conditions?
In well-fed state (when the substrates are available)
When the cholesterol supply is low
Synthesis of Cholesterol occurs in the…
Hepatocytes
Synthesis of Cholesterol in Hepatocytes
- Conversion of Acetyl CoA to HMG CoA
- via HMG CoA synthase - Synthesis of mevalonate
- via HMG-CoA reductase
- RATE LIMITING
- inhibited by station drugs - Conversion of mevalonate to isoprenyl pyrophosphates the loss of CO2
- Conversion of isoprenylpyrophosphosphates to squalene
- Conversion to squalene to lanosterol
- Conversion of Lanosterol to cholesterol
What is the rate limiting step of Synthesis of Cholesterol?
Synthesis of Mevalonate
What is cholesterol synthesis inhibited by?
Statin drugs
How many molecules of Mevalonate and Acetyl CoA are required for Cholesterol Synthesis?
For 1 cholesterol molecule
6 molecules of Mevalonate
18 molecules of Acetyl CoA
What enzyme regulates Cholesterol Synthesis?
HMG CoA Reductase.
Of stage 2, synthesis of Mevalonate
What part of the cell does cholesterol synthesis occur?
Cytoplasm. Intermediates must be charged to make them soluble. Associated with carrier proteins.
Regulation of Cholesterol Synthesis via HMG CoA Reductase
Sterol dependent regulation of the levels of the enzyme protein product
Sterol independent covalent modifications - phosphorylation/dephosphorylation
Hormonal regulation